Urine-based liquid biopsy: non-invasive and sensitive AR-V7 detection in urinary EVs from patients with prostate cancer

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Title
Urine-based liquid biopsy: non-invasive and sensitive AR-V7 detection in urinary EVs from patients with prostate cancer
Author(s)
Hyun-Kyung Woo; Juhee Park; Ja Yoon Ku; Chan Ho Lee; Vijaya Sunkara; Hong Koo Ha; Yoon-Kyoung Cho
Publication Date
2019-01
Journal
LAB ON A CHIP, v.19, no.1, pp.87 - 97
Publisher
The Royal Society of Chemistry
Abstract
Androgen-receptor splice variant 7 (AR-V7) is associated with castration-resistant prostate cancer (CRPC) and resistance to anti-androgen therapy. Despite its clinical importance, the lack of efficient methods for AR-V7 analysis remains a challenge for broader use of this biomarker in routine clinical practice. Herein, we suggest a practical and non-invasive liquid biopsy method for analysis of AR-V7 in the RNA of urine-derived extracellular vesicles (EVs) without the need for blood withdrawal. Urine-derived EVs were isolated by a lab-on-a-disc integrated with six independent nanofiltration units (Exo-Hexa) allowing simultaneous processing of six individual samples. Rapid enrichment of EVs (<30 min) from each 4 mL urine sample was followed by mRNA extraction, and AR-V7 and androgen receptor full-length (AR-FL) mRNA levels in the urinary EVs were quantified by droplet digital polymerase chain reaction (ddPCR) as absolute concentrations (copies per mL). Higher AR-V7 and lower AR-FL expressions were detected in urine-derived EVs from 14 patients with CRPC than in those from 22 patients with hormone-sensitive prostate cancer. Additionally, we found that AR-V7 transcript levels and the AR-V7/AR-FL ratio in urinary EVs were higher in patients with advanced prostate cancer. This study is the first to report that RNA of urine-derived EVs is a reliable source for AR-V7 expression analysis. The proposed method for quantifying AR-V7 in urinary EVs prepared by a lab-on-a-disc is therefore a simple and promising approach to liquid biopsy with great potential for therapeutic impact on prostate cancer. © The Royal Society of Chemistry 2019
URI
https://pr.ibs.re.kr/handle/8788114/5734
ISSN
1473-0197
Appears in Collections:
Center for Soft and Living Matter(첨단연성물질 연구단) > Journal Papers (저널논문)
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